Correlates to barrier function before and after dupilumab treatment

Summary: Abstract Body: We evaluated the association of transepidermal water loss(TEWL) with S. aureus(SA) abundance, blood biomarkers or atopic dermatitis(AD) severity and compared lesional(L) to nonlesional(NL) TEWL using data from the Atopic Dermatitis Research Network RDBPC dupilumab(DPL) trial. TEWL(Aquaflux) was measured in moderate-severe (IGA≥3) AD adults at Day(D)0 (n=60) and D42 (DPL n=32; placebo [PLA] n=18). Subjects were washed out of all AD treatments. NL site was 4 cm from a lesion; adjacent NL and L sites were swabbed for SA. At D0, TEWL varied widely at NL (median g/m2/h [IQR]; 15 [12-23]) and L (36 [25-47]) sites. TEWL did not differ by sex or race. Only NL TEWL negatively correlated with age (r=-0.317, p=0.014), and positively correlated with NL SA abundance (qPCR [r=0.308; p=0.017], colony counts/cm2 [r=0.322; p=0.012]), serum biomarkers (LDH [r=0.318; p=0.014], CCL17 [r=0.285; p=0.028] and s-CD25 [r=0.267; p=0.041]). Neither L nor NL TEWL associated with eosinophil counts or severity (pruritus NRS, EASI, SCORAD). We previously found that DPL significantly reduced L TEWL by D42. We extended that analysis to study the mean D42 L TEWL-D0 NL TEWL difference (controlling for D0 NL TEWL), which was smaller in DPL vs PLA (4.7 vs 16.8, p=0.001). Regardless of treatment, higher D0 NL TEWL was associated with smaller D42 L–D0 NL differences (p=0.006). Barrier function is highly variable in AD subjects and the major drivers of this abnormality remain uncertain, though the strongest associations are seen with NL TEWL. We observed that L approached D0 NL barrier with DPL at D42. Ellen Chinchilli¹, Takeshi Yoshida¹, Mark Boguniewicz², Tissa Hata³, Zelma Chiesa Fuxench⁴, Eric Simpson⁵, Justin Ko⁶, Peck Ong⁷, Samuel Kilgore⁸, Gloria David⁹, Michael Nodzenski⁹, Patrick Schlievert⁸, Wendy Davidson¹⁰, Donald Leung², Anna De Benedetto¹, Julie Ryan Wolf¹, Lisa Beck¹ 1. University of Rochester Medical Center, Rochester, NY, United States. 2. National Jewish Health, Denver, CO, United States. 3. University of California San Diego, La Jolla, CA, United States. 4. University of Pennsylvania, Philadelphia, PA, United States. 5. Oregon Health & Science University, Portland, OR, United States. 6. Stanford Medicine, Stanford, CA, United States. 7. Children's Hospital Los Angeles, Los Angeles, CA, United States. 8. University of Iowa, Iowa City, IA, United States. 9. Rho, Durham, NC, United States. 10. National Institutes of Health, Bethesda, MD, United States. Clinical Research: Interventional Research